endocrine disease
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Endocrine disease
Prepared by: Siti Norhaiza Binti Hadzir
Introduction• Endocrinology- the study of hormones,
which are secreted from specialized glands into the blood to influence the activity of cells at distance sites in the body.
Types of Hormones
• Peptides or proteins- hypothalamic factor (thyrotrophin releasing hormones), and pituitary gonadotropin.
• Amino acid derivatives- e.g thyroid hormones and adrenaline
• Steroid hormones- derivatives from cholesterol (e.g estrogen)
Measurement of Hormones
• Radioimmunoassay• Monoclonal antibodies
Endocrine Disease• Described as over or under secretion of
hormones• Failure of hormones responsiveness
OversecretionCushing’s disease where a pituitary adenoma secretes ACTH UnderscretionPrimary hypothyroidism where the thyroid gland is unable to make sufficient thyroid hormone despite continued stimulation by TSH
Failure of hormone responsivenessPseudohypoparathyroidism where pt become hypocalcemic despite elevated plasma PTH concentration because target organs lack a functioning receptor signaling mechanism
Examples of Endocrine Disease
The Pituitary Gland• The location• Anterior pituitary-hormone secreted• Posterior pituitary-hormone secreted• Hypersecretion-tumours (prolactin
secreting adenoma the most common)• Hypopituitarism-is uncommon; the clinical
presentation depends on the age, sex or the person.
Growth disorders• Growth in children can be divided into 3 i) rapid growth-1st 2 years –condition in
utero and nutrition ii) Steady growth-around 9 years-mainly
controlled by GH iii) puberty- sex hormones and GH-Other hormones involve in growth
Growth hormone insufficiency
• Is a rare cause of impaired physical growth.
• Test of GH insufficiency: - serum GH in response to exercise,
nocturnal sample - Stimulant (clonidine)• Treatment: genetically engineered GH for
children
Excessive growth• Extremely rapid linear growth (gigantism).
The condition is rare often due to pituitary tumor.
• Other causes; congenital adrenal hyperplasia, hyperthyroidism, inherited disorders.
• ↑GH later in life-Acromegaly due to pituitary adenoma
Diagnosis of Acromegaly• OGTT- a normal person will suppress GH
in plasma in response to glucose load.• Acromegaly-not suppress• ↑ IGF 1 • Treatment-surgery, radiotherapy, drugs
(octreotide-somastostatin analogue) and bromocriptine
The Thyroid Gland• The location• Thyroid hormone- thyroxine (T4) and tri-
iodothyronine (T3).• Most cells capable of taking up T4 and
deiodinating to the more biologically active T3.
• It is T3 which binds to receptors and triggers the end-organ effects of the thyroid hormones.
• T4 can be metabolized to reverse T3 (inactive)
Thyroid Hormone Action• Essential for the normal maturation and
metabolism of all the tissues in the body.
Plasma concentrationTotal (nmol/L) free (pmol/L)
Extent of protein binding
Half life (days)
T4 60-144 9.0-26.0 99.98 6-7
T3 1.0-2.9 3.0-9.0 99.66 1-1.5
Thyroid hormones in blood
Regulation of thyroid hormones
Hypothalamus
Anterior pituitary
Thyroid
TRH
TSH
T4 + T3
+
+
_
_
Thyroid Function Test• TSH (thyroid stimulating hormone)• Total T4 (bound hormone + free)• Free T4• TBG level• Free T3• Total T3 (bound hormone + free)• Titre of auto-antibodies to thyroid tissue
antigens
TRH test
• Involves intravenous injection of TRH and the measurement of pituitary TSH secreted in response to the stimulation.
• Purposes: i) Investigation of pituitary disorders ii) Investigation of hyperthyroidism
TSH
20 60Time (minutes)
TRH
TSH
20 60Time (minutes)
TRH
Normal response
Hyperthyroidism
Normal response
Secondary (pituitary) hypothyroid
Primary hypothyroid
Pituitary responses to TRH
Goitre• A goitre is an enlarged thyroid gland.• This may be associated with
hypofunction, hyperfunction or indeed normal concentrations of thyroid hormones in blood.
Hypothyroidism• 90% of cases of hypothyroidism occur as
a consequence of: - autoimmune destruction of the thyroid
gland (Hashimoto’s disease) - radioiodine or surgical treatment of
hyperthyroidism
Diagnosis of Hypothyroidism• Hypothyroidism is caused by a deficiency of thyroid hormones.• Primary hypothyroidism – failure of the
thyroid organ itself-elevated TSH concentration is diagnostic
• Secondary hypothyroidism-failure of pituitary to secrete TSH (less common).
• Treatment- thyroxine (tablet) therapy.
Non-thyroidal Illness• In systemic illness the normal regulation of
TSH, T4 and T3 secretion and subsequently metabolism of the thyroid hormones, is disturbed.
• ↑ T4 are converted to the reverse T3.• Reduction in thyroid hormone activity does
not result in an increased serum TSH concentration.
• TSH secretion is suppressed→ ↓ T4 and T3.• TBG decrease
Neonatal Hypothyroidism• The failure of the thyroid gland to develop
properly during early embryonic growth.• Children develop irreversible mental
retardation and characteristic feature of cretinism.
• The screening test- ↑ blood TSH concentration.
Hyperthyroidism• Hyperthyroidism can be result from: - Graves’ disease, diffuse toxic goitre - Toxic multinodular goitre - solitary toxic adenoma - thyroiditis - exogenously administered iodine and
iodine- containing drugs, e.g amiodarone - excessive T4 and T3 ingestion
Graves’ disease• An autoimmune disease in which
antibodies to the TSH receptor on the surface of the thyroid cells appear to mimic the action of the pituitary hormones.
• The normal regulatory controls on T4 synthesis and secretion are lacking.
• Pituitary secretion of TSH is completely inhibited by the ↑ conc. of thyroid hormones in the blood-eyelid retraction
Diagnosis
• Suppressed TSH concentration,↑ T4 and T3- primary hyperthyriodism
• Occasionally, biochemical confirmation of suspected hyperthyroidism will prove more difficult e.g in pregnancy.
Pt T4 nmol/L55-144)
T3 nmol/L(0.9-2.8)
TSH mU/L(0.35-5.0)
TBG mg/L (12-30)
Free T4 pmol/L(9-24)
Comment
1 130 2.0 3.4 25 18 Euthyroid
2 175 3.6 1.1 35 14 Euthyroid
3 190 5.0 <0.05 36 30 Hprthyroid
Thyroid hormone and binding protein results in pregnancy
Treatment• Anti-thyroid drugs (such as carbimazole
and propylthiouracil)- younger patient• Radioiodine-therapy with sodium I131is
commonly used in older pt. Most will require eventually require replacement thyroxine.
• Surgery-thyroidectomy
Thank you
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